Brief Reports
Copyright ©The Author(s) 1998. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 1998; 4(3): 266-267
Published online Jun 15, 1998. doi: 10.3748/wjg.v4.i3.266
Expression of nm23 gene in hepatocellular carcinoma tissue and its relation with metastasis
Bei Huang, Zhong-Bi Wu, You-Bing Ruan
Bei Huang, Zhong-Bi Wu, You-Bing Ruan, Department of Ultrastructural Pathology, Research Center of Experimental Medicine, Tongji Medical University, Wuhan 430030, Hubei Province, China
Bei Huang, female, was born on Feb. 13, 1964 and graduated from Tongji Medical University in 1987.
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Bei Huang, Department of Ultrastructural Pathology, Research Center of Experimental Medicine, Tongji Medical University, Wuhan 430030, Hubei Province, China
Telephone: +86-27-3692639
Received: September 10, 1997
Revised: December 20, 1997
Accepted: February 24, 1998
Published online: June 15, 1998

Key Words: liver neoplasms, carcinoma, hepatocellular, nm23 gene, gene expression, neoplasm metastasis, immunohistochemistry


Among the mostly expressed 23 genes in nonmetastatic tumors, nm23 had the highest frequency. Steeg et al[1] first identified and cloned its complementary DNA and confirmed that its lower expression was related to the high metastatic activity of melanoma cell lines. Many studies found afterwards that the expression of nm23 at the RNA or protein level was inversely correlated with the development of metastasis or poor clinical course in cohorts of several human tumor types, including breast, colorectal and gastric carcinomas. But the effects of nm23 on metastasis of hepatocellular carcinoma (HCC) is still unclear. In this study we have investigated nm23 expression in HCC with immunohistochemical techniques and the correlation between its expression level and metastatic progression.


Specimens of 24 cases of human HCC were obtained from surgical resections in Tongji Hospital. Observations were carried out on tissues from tumor areas, nonneoplastic areas and their boundary areas when available. Ten of them showed cancer cell emboli in portal vein or metastasis in portal lymph nodes or in distant organs, e.g. in the lung. Fourteen cases without metastasis were characterized by no findings of tumor invasion into the surrounding tissues at operation or no metastasis outside the liver by X-ray and sonography. The samples were fixed with 4% paraformaldehyde and embedded with paraffin. Successive sections were stained with HE, as well as immunohistochemically with the SP method. The staining was considered negative (-) when no cells were stained on the section, and weakly (+), moderately (+ +) and strong (+ + +) positive, when a few, more and a lot of cancer cells were darkly stained, respectively.


The positive signal revealed brown grains in cytoplasm of tumor cells.nm23protein expressed highly in HCC, but was not obviously related to the degree of malignancy histologically. The positive rate was 67% (16/24). The expression of nm23 was heterogeneitic in different cancer cell nodules and in the same nodule. The positive cells presented focal distribution or scattered through the cancer nodules. nm23 protein also expressed in the normal liver tissues around the carcinoma. The positive rate of nm23 was 86% in the group without metastasis, and 40% in the group with metastasis. The nm23 expression levelin metastatic HCC was significantly lower than that in nonmetastatic HCC (P < 0.05, Table 1).

Table 1 Relationship between nm23 expression and metastasis of HCC.
Groupsnnm23 expression
Positive rate (%)
-++ ++ + +

nm23 is a suppressor gene for tumor metastasis that encodes nucleoside diphosphokinase (NDPK). NDPK causes activation of a G protein pathway involved in the signal transduction of many growth factors and hormones. Expression of nm23 at the RNA or protein level was shown to be inversely correlated with the staging and differentiation of human breast cancer. In later period of poorly differentiated tumors, nm23 showed in general a lower expression and their recidive rate was higher, and survival rate was low[2]. Similar results were obtained by prostate and thyroid carcinoma[3]. Our data showed that the expression level of nm23 was significantly lower in cases of HCC with metastasis than that without metastasis, suggesting that nm23 had some effects of inhibiting metastasis of HCC. However, no relation between expression of nm23 and lymph node metastasis was reported by Haut et al[4]. However, Cohn et al[5] found that nm23 was associated with distant metastasis after operation in colorectal carcinoma. Moreover, nm23 was reported to be related with lymph node metastasis in pulmonary squamous cell carcinoma, but not in pulmonary adenocarcinoma. Our preliminary study also showed that there was no nm23 expression in 2 nonmetastatic HCC tissues, but stronger expression in 1 metastatic HCC. These suggested that some other regulatory factors may exist evidently in the process of metastasis of HCC.


Project supported by the National Natural Science Foundation of China, No. 39070376

1.  Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta LA, Sobel ME. Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst. 1988;80:200-204.  [PubMed]  [DOI]
2.  Hennessy C, Henry JA, May FE, Westley BR, Angus B, Lennard TW. Expression of the antimetastatic gene nm23 in human breast cancer: an association with good prognosis. J Natl Cancer Inst. 1991;83:281-285.  [PubMed]  [DOI]
3.  Konishi N, Nakaoka S, Tsuzuki T, Matsumoto K, Kitahori Y, Hiasa Y, Urano T, Shiku H. Expression of nm23-H1 and nm23-H2 proteins in prostate carcinoma. Jpn J Cancer Res. 1993;84:1050-1054.  [PubMed]  [DOI]
4.  Haut M, Steeg PS, Willson JK, Markowitz SD. Induction of nm23 gene expression in human colonic neoplasms and equal expression in colon tumors of high and low metastatic potential. J Natl Cancer Inst. 1991;83:712-716.  [PubMed]  [DOI]
5.  Cohn KH, Wang FS, Desoto-LaPaix F, Solomon WB, Patterson LG, Arnold MR, Weimar J, Feldman JG, Levy AT, Leone A. Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma. Lancet. 1991;338:722-724.  [PubMed]  [DOI]